Cells divide and grow by their own regulation system, and they maintain balance of the overall number in a body by apoptosis, which occurs when cells reach their lifespan or get damaged. However, uncontrolled proliferation of cells due to failure of cells' own regulation system may cause an invasion of the cells into adjacent normal tissues and organs to form a tumor, thereby destroying or distorting the normal tissues and organs. This state is called cancer. Cancer therapies include surgery, radiotherapy, chemotherapy, and so on, but, several problems such as low cure rates and many side effects, etc. have been reported. Thus, a development of new anticancer drug that can reduce the side effects and increase the cure rates is required.
It is known that the incidence of pancreatic cancer is low compared with other cancers, but it has the highest mortality among cancer patients. The mortality of the pancreatic cancer is increasing because of difficulty in early diagnosis and easy metastasis to the surrounding organs or lymph nodes.
Chemotherapy and radiotherapy are used to treat the pancreatic cancer. Gemcitabine, which is most widely used anti-pancreatic cancer drug, is used with other drugs such as oxalate, 5-FU (5-fluorouracil), and so on. However, it does not have much effect on significant increase of the survival rate of pancreatic cancer patients.
Recently, research is being carried out to treat various disorders by using an RNA oligonucleotide. U.S. Patent Application Publication No. 2012/0288476 discloses that an uncapped oligonucleotide having a phosphate group at the 5′-end can increase the expression of type 1 interferon, interleukin-18, and interleukin-1β, etc.
In addition, U.S. Patent Application Publication No. 2012/0121551 discloses that an RNA consisting of four nucleotides can promote immune responses by inducing the activation of interferon-α.
The RNAs mentioned above have a common feature that they all have a triphosphate group at the 5′-end. It has been known in the art that an uncapped RNA which has a triphosphate group at the 5′-end can activate the expression of interferon by binding to intracellular retinoic acid-inducible gene-I (RIG-I) protein.
Interferon is a glycoprotein derived from most of the cells having a nucleus. Interferon was known as an important factor in suppressing tumor growth since it was reported that interferon-α and interferon-β genes of type 1 interferon gene cluster were deleted in tumor cells. Recombinant interferon-β has been used as an anticancer drug from the 1980s (Jun Yoshida et al., Cancer Sci., 2004, Vol. 95, No. 11, 858-865).